AGK2

304896-28-4

434.27

DMSO : 6 mg/mL (13.82 mM; Need ultrasonic and warming)

Apoptosis; Epigenetics; Cell Cycle/DNA Damage

AGK2 is a selective SIRT2 inhibitor with an IC₅₀ of 3.5 uM. AGK2 inhibits SIRT1 and SIRT3 with IC₅₀s of 30 and 91 uM, respectively. IC50 & Target: IC50: 3.5 uM (SIRT2), 30 uM (SIRT1), 91 uM (SIRT3)^[1] In Vitro: AGK2 significantly inhibits cell proliferation in a dose-dependent manner. AGK2 also significantly inhibits cell growth in a dose-dependent manner without inducing cytotoxicity at low doses. Twelve days after AGK2 (5 uM) treatment, cells show a significantly reducing colony forming ability in soft agar to 46% of the control cells. Western blot analysis shows that the levels of CDK4 or CDK6 and cyclin D1 are decreased after AGK2 treatment in a dose-dependent manner. In addition, AGK2 inhibits the expression of p53 protein^[2]. Treatment of microglial BV2 cells with 10 uM AGK2 leads to a significant increase in PAR signals. Treatment of microglial BV2 cells with 10 uM AGK2 also leads to a significant decrease in the intracellular ATP and significant increases in both late-stage apoptosis and necrosis of the cells^[3]. In Vivo: AGK2 significantly reduces mortality and decreases levels of cytokines in blood (TNF-alpha: 298.3+/-24.6 vs 26.8+/-2.8 pg/mL, p=0.0034; IL-6: 633.4+/-82.8 vs 232.6+/-133.0 pg/mL, p=0.0344) and peritoneal fluid (IL-6: 704.8+/-67.7 vs 391.4+/-98.5 pg/mL, p=0.033) compare to vehicle control. AGK2 also suppresses the TNF-alpha and IL-6 production in the culturing splenocytes (TNF-alpha: 68.1+/-6.4 vs 23.9+/-2.8 pg/mL, p=0.0009; IL-6: 73.1+/-4.2 vs 49.6+/-3.0 pg/mL; p=0.0051)^[4].